Log in

Adrenal Metastasectomy in the Era of Immuno- and Targeted Therapy

  • Endocrine Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Adrenal metastasectomy has an increasing role in multimodality oncologic care for diverse primary cancer types. In this review, we discuss the epidemiology, evaluation, and contemporary best practices in the management of adrenal metastases from various primaries. Initial evaluation of suspected adrenal metastases should include diagnostic imaging to assess the extent of tumor involvement and determine surgical resectability, as well as biochemical evaluation for hormone secretion. Biopsy has a minimal role and should only be performed in tumors that are established to be non-hormone secreting and when the biopsy results would change clinical management. Adrenal metastasectomy is associated with survival benefit in selected patients. We suggest that adrenal metastasectomy has the greatest benefit in four clinical scenarios: (1) disease limited to the adrenal gland in which adrenalectomy renders the patient disease-free; (2) isolated progression in the adrenal gland in the setting of otherwise controlled metastatic extra-adrenal disease; (3) need for palliation of symptoms related to adrenal metastases; or (4) in the context of tissue-based clinical trials. Both minimally invasive and open adrenalectomy techniques are safe and appear to have equivalent oncologic outcomes. Minimally invasive approaches are favored when technically feasible while maintaining oncologic principles. A multidisciplinary evaluation including clinicians with expertise in the primary cancer type is essential to the successful management of adrenal metastases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Thailand)

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Nelson DW, Fischer TD, Graff-Baker AN, et al. Impact of effective systemic therapy on metastasectomy in stage IV Melanoma: a matched-pair analysis. Ann Surg Oncol. 2019;10(10):019–07487.

    Google Scholar 

  2. Tomlinson JS, Jarnagin WR, DeMatteo RP, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575–80. https://doi.org/10.1200/JCO.2007.4511.0833.

    Article  PubMed  Google Scholar 

  3. Saxena A, Chua TC, Sarkar A, et al. Progression and survival results after radical hepatic metastasectomy of indolent advanced neuroendocrine neoplasms (NENs) supports an aggressive surgical approach. Surgery. 2011;149(2):209–20. https://doi.org/10.1016/j.surg.2010.1006.1008.

    Article  PubMed  Google Scholar 

  4. Meimarakis G, Ruttinger D, Stemmler J, et al. Prolonged overall survival after pulmonary metastasectomy in patients with breast cancer. Ann Thorac Surg. 2013;95(4):1170–80. https://doi.org/10.1016/j.athoracsur.2012.1111.1043.

    Article  PubMed  Google Scholar 

  5. Bartlett EK, Simmons KD, Wachtel H, et al. The rise in metastasectomy across cancer types over the past decade. Cancer. 2015;121(5):747–57. https://doi.org/10.1002/cncr.29134.

    Article  PubMed  Google Scholar 

  6. Lam KY, Lo CY. Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. Clin Endocrinol (Oxf). 2002;56(1):95–101.

    PubMed  Google Scholar 

  7. Zeiger MA, Thompson GB, Duh QY, et al. The American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons medical guidelines for the management of adrenal incidentalomas. Endocr Pract. 2009;15(Suppl 1):1–20.

    PubMed  Google Scholar 

  8. Wachtel H, Roses RE, Kuo LE, et al. Adrenalectomy for secondary malignancy: patients, outcomes, and indications. Ann Surg. 2021;274(6):1073–80.

    PubMed  Google Scholar 

  9. Mao JJ, Dages KN, Suresh M, Bancos I. Presentation, disease progression and outcomes of adrenal gland metastases. Clin Endocrinol (Oxf). 2020;93(5):546–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Dinnes J, Bancos I, di Ferrante Ruffano L, et al. Management of endocrine disease: imaging for the diagnosis of malignancy in incidentally discovered adrenal masses: a systematic review and meta-analysis. Eur J Endocrinol. 2016;175(2):51–64.

    Google Scholar 

  11. Iñiguez-Ariza NM, Kohlenberg JD, Delivanis DA, et al. Clinical, biochemical, and radiological characteristics of a single-center retrospective cohort of 705 large adrenal tumors. Mayo Clin Proc Innov Qual Outcomes. 2018;2(1):30–9.

    PubMed  Google Scholar 

  12. Delivanis DA, Bancos I, Atwell TD, et al. Diagnostic performance of unenhanced computed tomography and (18) F-fluorodeoxyglucose positron emission tomography in indeterminate adrenal tumours. Clin Endocrinol (Oxf). 2018;88(1):30–6.

    PubMed  Google Scholar 

  13. Kim JY, Kim SH, Lee HJ, et al. Utilisation of combined 18F-FDG PET/CT scan for differential diagnosis between benign and malignant adrenal enlargement. Br J Radiol. 2013;86(1028):20130190.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Platzek I, Sieron D, Plodeck V, Borkowetz A, Laniado M, Hoffmann RT. Chemical shift imaging for evaluation of adrenal masses: a systematic review and meta-analysis. Eur Radiol. 2019;29(2):806–17.

    PubMed  Google Scholar 

  15. Yip L, Duh QY, Wachtel H, et al. American association of endocrine surgeons guidelines for adrenalectomy: executive summary. JAMA Surg. 2022;157(10):870–7.

    PubMed  Google Scholar 

  16. Bancos I, Tamhane S, Shah M, et al. Diagnosis of endocrine disease: the diagnostic performance of adrenal biopsy: a systematic review and meta-analysis. Eur J Endocrinol. 2016;175(2):R65-80.

    CAS  PubMed  Google Scholar 

  17. Mody MK, Kazerooni EA, Korobkin M. Percutaneous CT-guided biopsy of adrenal masses: immediate and delayed complications. J Comput Assist Tomogr May-Jun. 1995;19(3):434–9.

    CAS  Google Scholar 

  18. Chou JF, Row D, Gonen M, Liu YH, Schrag D, Weiser MR. Clinical and pathologic factors that predict lymph node yield from surgical specimens in colorectal cancer: a population-based study. Cancer. 2010;116(11):2560–70.

    PubMed  Google Scholar 

  19. Drake FT, Beninato T, **ong MX, et al. Laparoscopic adrenalectomy for metastatic disease: retrospective cohort with long-term, comprehensive follow-up. Surgery. 2019;165(5):958–64.

    PubMed  Google Scholar 

  20. Goujon A, Schoentgen N, Betari R, et al. Prognostic factors after adrenalectomy for adrenal metastasis. Int Urol Nephrol. 2020;52(10):1869–76.

    CAS  PubMed  Google Scholar 

  21. Krumeich LN, Roses RE, Kuo LE, et al. Survival after adrenalectomy for metastatic lung cancer. Ann Surg Oncol. 2022;29(4):2571–9.

    PubMed  Google Scholar 

  22. Mittendorf EA, Lim SJ, Schacherer CW, et al. Melanoma adrenal metastasis: natural history and surgical management. Am J Surg. 2008;195(3):363–8.

    PubMed  Google Scholar 

  23. Asare EA, Fisher SB, Chiang Y, Haydu LE, Patel SH, Keung EZ, Lucci A, Wargo J, Gershenwald JE, Ross MI, Lee JE. Melanoma Metastatic to the Adrenal Gland: An Update on the Role of Adrenalectomy in Multidisciplinary Management. Houston, TX: The University of Texas MD Anderson Cancer Center; 2023.

    Google Scholar 

  24. Russo AE, Untch BR, Kris MG, et al. Adrenal metastasectomy in the presence and absence of extraadrenal metastatic disease. Ann Surg. 2019;270(2):373–7.

    PubMed  Google Scholar 

  25. Kiernan CM, Lee JE. Minimally invasive surgery for primary and metastatic adrenal malignancy. Surg Oncol Clin N Am. 2019;28(2):309–26.

    PubMed  Google Scholar 

  26. Romero Arenas MA, Sui D, Grubbs EG, Lee JE, Perrier ND. Adrenal metastectomy is safe in selected patients. World J Surg. 2014;38(6):1336–42.

    PubMed  Google Scholar 

  27. Strong VE, D’Angelica M, Tang L, et al. Laparoscopic adrenalectomy for isolated adrenal metastasis. Ann Surg Oncol. 2007;14(12):3392–400.

    PubMed  Google Scholar 

  28. Dickson PV, Kim L, Yen TWF, et al. Evaluation, staging, and surgical management for adrenocortical carcinoma: an update from the SSO endocrine and head and neck disease site working group. Ann Surg Oncol. 2018;25(12):3460–8.

    PubMed  Google Scholar 

  29. Glenn JA, Kiernan CM, Yen TW, et al. Management of suspected adrenal metastases at 2 academic medical centers. Am J Surg. 2016;211(4):664–70.

    PubMed  Google Scholar 

  30. Baghai M, Thompson GB, Young WF Jr, Grant CS, Michels VV, van Heerden JA. Pheochromocytomas and paragangliomas in von Hippel-Lindau disease: a role for laparoscopic and cortical-sparing surgery. Arch Surg. 2002;137(6):682–8 (discussion 688-689).

    PubMed  Google Scholar 

  31. Neumann HPH, Tsoy U, Bancos I, et al. Comparison of pheochromocytoma-specific morbidity and mortality among adults with bilateral pheochromocytomas undergoing total adrenalectomy vs cortical-sparing adrenalectomy. JAMA Netw Open. 2019;2(8):e198898.

    PubMed  PubMed Central  Google Scholar 

  32. Moreno P, de la Quintana BA, Musholt TJ, et al. Laparoscopy versus open adrenalectomy in patients with solid tumor metastases: results of a multicenter European study. Gland Surg. 2020;9(Suppl 2):S159–65. https://doi.org/10.21037/gs.22019.21010.21015.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zerrweck C, Caiazzo R, Clerquin B, et al. Renal origin and size are independent predictors of survival after surgery for adrenal metastasis. Ann Surg Oncol. 2012;19(11):3621–6.

    PubMed  Google Scholar 

  34. Vlk E, Ebbehoj A, Donskov F, et al. Outcome and prognosis after adrenal metastasectomy: nationwide study. BJS Open. 2022;6(2):zrac047.

    PubMed  PubMed Central  Google Scholar 

  35. Ramsingh J, O’Dwyer P, Watson C. Survival outcomes following adrenalectomy for isolated metastases to the adrenal gland. Eur J Surg Oncol. 2019;45(4):631–4.

    PubMed  Google Scholar 

  36. Metman MJH, Viëtor CL, Seinen AJ, et al. Outcomes after surgical treatment of metastatic disease in the adrenal gland; valuable for the patient? Cancers (Basel). 2021;14(1):156.

    PubMed  PubMed Central  Google Scholar 

  37. Moreno P, de la Quintana BA, Musholt TJ, et al. Adrenalectomy for solid tumor metastases: results of a multicenter European study. Surgery. 2013;154(6):1215–22 (discussion 1222-1213).

    PubMed  Google Scholar 

  38. Gulati S, Vaishampayan U. Current state of systemic therapies for advanced renal cell carcinoma. Curr Oncol Rep. 2020;22(3):26.

    PubMed  Google Scholar 

  39. Flaherty DC, Deutsch GB, Kirchoff DD, et al. Adrenalectomy for metastatic melanoma: current role in the age of nonsurgical treatments. Am Surg. 2015;81(10):1005–9.

    PubMed  PubMed Central  Google Scholar 

  40. Borgers JSW, Tobin RP, Torphy RJ, et al. Melanoma metastases to the adrenal gland are highly resistant to immune checkpoint inhibitors. J Natl Compr Canc Netw. 2021. https://doi.org/10.6004/jnccn.2020.7800.

    Article  PubMed  Google Scholar 

  41. Luketich JD, Burt ME. Does resection of adrenal metastases from non-small cell lung cancer improve survival? Ann Thorac Surg. 1996;62(6):1614–6.

    CAS  PubMed  Google Scholar 

  42. Porte H, Siat J, Guibert B, et al. Resection of adrenal metastases from non-small cell lung cancer: a multicenter study. Ann Thorac Surg. 2001;71(3):981–5.

    CAS  PubMed  Google Scholar 

  43. Mercier O, Fadel E, de Perrot M, et al. Surgical treatment of solitary adrenal metastasis from non-small cell lung cancer. J Thorac Cardiovasc Surg. 2005;130(1):136–40.

    PubMed  Google Scholar 

  44. Pfannschmidt J, Schlolaut B, Muley T, Hoffmann H, Dienemann H. Adrenalectomy for solitary adrenal metastases from non-small cell lung cancer. Lung Cancer. 2005;49(2):203–7.

    PubMed  Google Scholar 

  45. Bastian S, Clerici T, Neuweiler J, Cerny T, Früh M. Surgical resection of isolated adrenal metastases in patients with non-small cell lung cancer: a single-institution experience and review of the literature. Onkologie. 2011;34(12):665–70.

    PubMed  Google Scholar 

  46. Tanvetyanon T, Robinson LA, Schell MJ, et al. Outcomes of adrenalectomy for isolated synchronous versus metachronous adrenal metastases in non-small-cell lung cancer: a systematic review and pooled analysis. J Clin Oncol. 2008;26(7):1142–7.

    PubMed  Google Scholar 

  47. Gao XL, Zhang KW, Tang MB, Zhang KJ, Fang LN, Liu W. Pooled analysis for surgical treatment for isolated adrenal metastasis and non-small cell lung cancer. Interact Cardiovasc Thorac Surg. 2017;24(1):1–7.

    PubMed  Google Scholar 

  48. De Wolf J, Bellier J, Lepimpec-Barthes F, et al. Exhaustive preoperative staging increases survival in resected adrenal oligometastatic non-small-cell lung cancer: a multicentre study. Eur J Cardiothorac Surg. 2017;52(4):698–703.

    PubMed  Google Scholar 

  49. Palma DA, Salama JK, Lo SS, et al. The oligometastatic state - separating truth from wishful thinking. Nat Rev Clin Oncol. 2014;11(9):549–57.

    PubMed  Google Scholar 

  50. Baydoun A, Chen H, Poon I, et al. Outcomes and toxicities in oligometastatic patients treated with stereotactic body radiotherapy for adrenal gland metastases: a multi-institutional retrospective study. Clin Transl Radiat Oncol. 2022;33:159–64.

    CAS  PubMed  Google Scholar 

  51. Chen WC, Baal JD, Baal U, et al. Stereotactic body radiation therapy of adrenal metastases: a pooled meta-analysis and systematic review of 39 studies with 1006 patients. Int J Radiat Oncol Biol Phys. 2020;107(1):48–61.

    PubMed  PubMed Central  Google Scholar 

  52. Elmali A, Akkus Yildirim B, Cengiz M, et al. Stereotactic radiotherapy for adrenal metastases: a multi-institutional review of patient characteristics and outcomes—Turkish Society for Radiation Oncology SBRT Group Study (Trod SBRT 10–004). Oncol Res Treat. 2022;45(12):717–27.

    CAS  PubMed  Google Scholar 

  53. Franzese C, Stefanini S, Massaro M, et al. Phase II trial of stereotactic body radiation therapy on adrenal gland metastases: evaluation of efficacy and impact on hormonal production. J Cancer Res Clin Oncol. 2021;147(12):3619–25.

    CAS  PubMed  Google Scholar 

  54. Toesca DAS, Koong AJ, von Eyben R, Koong AC, Chang DT. Stereotactic body radiation therapy for adrenal gland metastases: outcomes and toxicity. Adv Radiat Oncol. 2018;3(4):621–9.

    PubMed  PubMed Central  Google Scholar 

  55. Eldaya RW, Paulino AC, Blanco AI, et al. Preservation of adrenal function after successful stereotactic body radiation therapy of metastatic renal cell carcinoma involving the remaining contralateral adrenal gland. Pract Radiat Oncol. 2012;2(4):270–3.

    PubMed  Google Scholar 

  56. Botsa EI, Thanou IL, Papatheodoropoulou AT, Thanos LI. Thermal ablation in the management of adrenal metastasis originating from non-small cell lung cancer: A 5-year single-center experience. Chin Med J (Engl). 2017;130(17):2027–32.

    PubMed  PubMed Central  Google Scholar 

  57. Frenk NE, Daye D, Tuncali K, et al. Local control and survival after image-guided percutaneous ablation of adrenal metastases. J Vasc Interv Radiol. 2018;29(2):276–84.

    PubMed  Google Scholar 

  58. Welch BT, Callstrom MR, Carpenter PC, et al. A single-institution experience in image-guided thermal ablation of adrenal gland metastases. J Vasc Interv Radiol. 2014;25(4):593–8.

    PubMed  Google Scholar 

  59. De Espinosa Ycaza AE, Welch TL, Ospina NS, et al. Image-guided thermal ablation of adrenal metastases: hemodynamic and endocrine outcomes. Endocr Pract. 2017;23(2):132–40.

    Google Scholar 

  60. Tetzlaff MT, Messina JL, Stein JE, et al. Pathological assessment of resection specimens after neoadjuvant therapy for metastatic melanoma. Ann Oncol. 2018;29(8):1861–8.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Support was provided to HW from the National Institutes of Health National Cancer Institute grant #K08 CA270385.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Heather Wachtel MD.

Ethics declarations

Disclosure

Heather Wachtel, Paxton Dickson, Sarah B. Fisher, Colleen M. Kiernan, and Carmen C. Solórzano declare no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wachtel, H., Dickson, P., Fisher, S.B. et al. Adrenal Metastasectomy in the Era of Immuno- and Targeted Therapy. Ann Surg Oncol 30, 4146–4155 (2023). https://doi.org/10.1245/s10434-023-13474-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-023-13474-8

Navigation